rs539748

Positions:

• chrX-114586876-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.-147+2217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (25533 hom., 25963 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

Genes affected

HTR2C (HGNC:5295): (5-hydroxytryptamine receptor 2C) This gene encodes a seven-transmembrane G-protein-coupled receptor. The encoded protein responds to signaling through the neurotransmitter serotonin. The mRNA of this gene is subject to multiple RNA editing events, where adenosine residues encoded by the genome are converted to inosines. RNA editing is predicted to alter the structure of the second intracellular loop, thereby generating alternate protein forms with decreased ability to interact with G proteins. Abnormalities in RNA editing of this gene have been detected in victims of suicide that suffer from depression. In addition, naturally-occuring variation in the promoter and 5' non-coding and coding regions of this gene may show statistically-significant association with mental illness and behavioral disorders. Alternative splicing results in multiple different transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.-147+2217C>T		intron_variant		ENST00000276198.6
HTR2C	NM_001256760.3	c.-238+2217C>T		intron_variant
HTR2C	NM_001256761.3	c.-147+2217C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.-147+2217C>T		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.-147+2217C>T		intron_variant		1
HTR2C	ENST00000371951.5	c.-238+2217C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 88767 AN: 109485 Hom.: 25545 Cov.: 22 AF XY: 0.817 AC XY: 25941 AN XY: 31743

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.789

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.831

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.811 AC: 88768 AN: 109520 Hom.: 25533 Cov.: 22 AF XY: 0.817 AC XY: 25963 AN XY: 31788

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.831

Alfa AF: 0.822 Hom.: 10656

Bravo AF: 0.800

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs539748; hg19: chrX-113821349;